Decarbonylative Transfer Hydrochlorination of Alkenes and Alkynes Based on a B(C6F5)3‐Initiated Grob Fragmentation

Abstract Readily available cyclohexa‐2,5‐dien‐1‐ylcarbonyl chloride derivatives are introduced as bench‐stable HCl surrogates for transfer hydrochlorination of terminal and internal alkenes as well as selected alkynes. The stepwise Grob fragmentation of those acyl chlorides into chloride, carbon monoxide, a low‐molecular‐weight arene, and a proton is promoted by B(C6F5)3. This decarbonylative transfer process enables the addition of HCl across C−C double and triple bonds with Markovnikov selectivity at room temperature.


Cyclohexa-2,5-diene-1-carboxylic Acid (5aa)
A 500-mL three-neck round bottom flask equipped with a dry ice condenser and a mechanical stirrer was flushed with N2 for 10 min before being placed in a dry ice/acetone bath (-78 °C). Ammonia (approx. 200 mL) was condensed, and a solution of benzoic acid (10.0 g, 81.9 mmol, 1.0 equiv) in THF (50 mL) was then added dropwise. Then, lithium (2.27 g, 328 mmol, 4.0 equiv) was added portionwise until the deep dark blue of the solution persisted. The mixture was stirred at -78 °C for 1 h, removed from the cold bath and allowed to stir at room temperature overnight for the evaporation of ammonia. Water (100 mL) was added, and the aqueous phase was acidified with HCl (37%, aq.) under ice bath until pH = 2 was achieved.
The mixture was extracted with Et2O (3 × 150 mL), and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with Et2O/n-pentane = 1:10 as the eluent to afford 5aa as a colorless oil (9.05 g, 89%). The NMR spectroscopic data are in accordance with those reported in the literature. [S2] Supporting Information for Angewandte Chemie International Edition S6

1-Methylcyclohexa-2,5-diene-1-carboxylic Acid (5ab)
Supporting Information for Angewandte Chemie International Edition S7 A 500-mL three-neck round bottom flask equipped with a dry ice condenser and a mechanical stirrer was flushed with N2 for 10 min before being placed in a dry ice/acetone bath (-78 °C). Ammonia (approx. 200 mL) was condensed, and a solution of benzoic acid (10.0 g, 81.9 mmol, 1.0 equiv) in THF (50 mL) was then added dropwise. Then, lithium (2.27 g, 328 mmol, 4.0 equiv) was added portionwise until the deep dark blue of the solution persisted. After the mixture was stirred at -78 °C for 1 h, iodomethane (20.4 mL, 328 mmol, 4.0 equiv) was added dropwise. After addition, the mixture was removed from the cold bath and allowed to stir at room temperature overnight for the evaporation of ammonia. Water (100 mL) was added, and the aqueous phase was acidified with HCl (37%, aq.) under ice bath until pH = 2 was achieved.
Ammonia (approx. 200 mL) was condensed, and a solution of 4-methylbenzoic acid (10.9 g, 80.0 mmol, 1.0 equiv) in THF (50 mL) was then added dropwise. Then, lithium (2.27 g, 328 mmol, 4.0 equiv) was added portionwise until the deep dark blue of the solution persisted. After the mixture was stirred at -78 °C for 1 h, iodomethane (19.9 mL, 320 mmol, 4.0 equiv) was added dropwise. After addition, the mixture was removed from the cold bath and allowed to stir at room temperature overnight for the evaporation of ammonia. Water (100 mL) was added, and the aqueous phase was acidified with HCl (37%, aq.) under ice bath until pH = 2 was achieved. The mixture was extracted with Et2O (3 × 150 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel with Et2O/n-pentane = 1:6 as the eluent to afford 5ac as a yellow oil (10.82 g, 89%). The NMR spectroscopic data are in Supporting Information for Angewandte Chemie International Edition S9 accordance with those reported in the literature. [S4]

General Procedure for the Synthesis of 1b-n and 1p
Scheme S4. Synthesis of alkene substrates.
According to a modified literature procedure, [S5] a dried Schlenk flask was charged with a solution of the indicated Grignard reagent (10.0 mmol, 1.0 equiv) in anhydrous THF (0.2M).
The solution is cooled to -30 °C, and 3-bromo-2-methylprop-1-ene (12.0 mmol, 1.2 equiv) was Supporting Information for Angewandte Chemie International Edition S11 added dropwise under nitrogen atmosphere. The reaction mixture is stirred at -30 °C for 1 h, then slowly warmed to room temperature and stirred overnight. After addition of saturated aqueous NH4Cl (15 mL), the mixture was extracted with tert-butyl methyl ether (3 × 20 mL).
The combined organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel to give the desired product.

General Procedure for the Decarbonylative Transfer Hydrochlorination
Method A (1.2 equiv of 2ab and 5.0 mol% of B(C6F5)3) In a glovebox, a 1.5-mL GLC vial equipped with a magnetic stir bar was charged with the indicated alkene or alkyne (1.0 equiv) and surrogate 2ab (1.2 equiv). CH2Cl2 (0.5 M) was added followed by the addition of B(C6F5)3 (5.0 mol%). The vial was capped, and the solution was stirred in the glovebox at room temperature for 3 h or 24 h (for 1g, 1n, 1t, 1u, and 1x). The reaction was then removed from the glovebox, filtered through a small column (covered with 2.0 cm silica gel) eluting with n-pentane or n-pentane/Et2O = 5:1 (for 3c, 3g, 3s, 3t, 3u, and 3x), and all volatiles were removed under reduced pressure to obtain the analytically pure alkyl or alkenyl chloride. If necessary, the crude product is purified by flash column chromatography on silica gel.
Method B (1.2 equiv of 2ab and 5.0 mol% of BCl3) For the substrates where the corresponding products are unstable towards silica gel.
In a glovebox, a 1.5-mL GLC vial equipped with a magnetic stir bar was charged with the indicated alkene (1.0 equiv) and surrogate 2ab (1.2 equiv). CH2Cl2 (0.5 M) was added followed by the addition of BCl3 (5.0 mol%, 1.0 M in toluene). The vial was capped, and the solution was stirred in the glovebox at room temperature for 3 h. The reaction was then removed from the glovebox, methanol (0.5 mL/mmol) was added to the mixture, and the mixture was stirred for 5 min. All volatiles were removed under reduced pressure to afford the analytically pure alkyl chloride.
Method C (3.0 equiv of 2ab and 20 mol% B(C6F5)3) In a glovebox, a 1.5-mL GLC vial equipped with a magnetic stir bar was charged with the indicated alkene (0.20 mmol, 1.0 equiv) and surrogate 2ab (3.0 equiv). CH2Cl2 (0.4 mL) was added followed by the addition of B(C6F5)3 (20 mol%). The vial was capped, and the solution was stirred in the glovebox at room temperature for 24 h. The reaction was then removed from the glovebox, filtered through a small column (covered with 2.0 cm silica gel) eluting with n-Supporting Information for Angewandte Chemie International Edition S13 pentane or n-pentane/Et2O = 5:1 (for 3a'), and all volatiles were removed under reduced pressure to obtain the analytically pure chloroalkane. If necessary, the crude product is purified by flash column chromatography on silica gel.
The reaction was then removed from the glovebox, methanol (0.1 mL) was added to the mixture, and the mixture was stirred for 5 min. All volatiles were removed under reduced pressure to afford the analytically pure alkyl chloride 3b'.
Method E (2.0 equiv of 2ab and 10 mol% of B(C6F5)3) In a glovebox, a 1.5-mL GLC vial equipped with a magnetic stir bar was charged with the indicated alkyne (1.0 equiv) and surrogate 2ab (2.0 equiv). CH2Cl2 (0.5 M) was added followed by the addition of B(C6F5)3 (10 mol%). The vial was capped, and the solution was stirred in the glovebox at room temperature for 24 h. The reaction was then removed from the glovebox, filtered through a small column (covered with 2.0 cm silica gel) eluting with n-pentane, and all volatiles were removed under reduced pressure to obtain the analytically pure alkenyl chloride. in accordance with those reported. [S20] 1-(2-Chloro-2-methylpropyl)-4-methylbenzene (3b